Abstract
We summarized mutations in human genes of lactate dehydrogenase (LDH) A (M) or B (H) subunits. In a collection of 19 analyzed cases, mutations were demonstrated in 13 (4 in A subunit and 9 in B subunit), including 3 transitions, 5 transversions and 5 deletions/duplications.
Four missense mutations causing LDH deficiency are located at a conserved sequence which are indispensable for the function of LDH molecule, such as the stability of P-axis, nicotinamide adenine dinucleotide (NAD)-binding and substratebinding, Two electrophoretic variants were identified to be due to missense mutations located at codon 6 or 314. These residues are not buried in the subunit molecules but located at the surface of protein. We used a computer model based upon Protein Data Bank to predict the location and function of point mutations of LDH.
Two nonsense mutations, two duplications (8 by and 4 bp) and two deletions (20 by and 1 bp) resulted in premature termination of LDH subunits. Because the premature termination induces serious perturbation and the instability of tertramer formation, the enzyme deficiency may be due principally to the more rapid in vivo denaturation degradation of the variant enzyme.
These mutations are different from each other except two mutations, which are 20 by deletion in exon 6 of LDH-A gene (5 families including 21 individuals) and a missense mutation in exon 4 of LDH-B gene (3 cases). It is concluded that there is considerable heterogeneity among genetic mutations of human LDH genes.
